Abstract: :
Purpose: Posterior capsule opacification (PCO) is a common complicationthat affects 30-50% of patients within two years after cataractsurgery. The proliferation of residual lens epithelial cells(LECs) after surgery is responsible for PCO. It most frequentlyoccurs following surgery in children with congenital cataracts.Actually PCO may be treated with YAG-capsulotomy. However thistreatment is expensive and presents some contre-indicationsin terms of costs, ocular complications, feasibility and efficacy.The authors describe preliminary results of a patented procedurebased on somatic gene therapy, which is intended to preventcell growth on the posterior capsule.Methods: Lens capsuleswere isolated from pig eyes, sterile PMMA capsular tension ringsinserted and the preparations placed in culture medium. Piglens capsules were then infected by a non-replicative recombinantadenovirus expressing the thymidine kinase from HSV1 (Ad-HSV1TK)or the green fluorescent protein (GFP) in a cell-specific manner.LEC-specific expression of the foreign genes delivered by therecombinant adenoviruses is achieved with one of three promoters:a Major Intrinsic Protein gene promoter (Ad-MIP-HSV1TK), a ßA3/A1-crystallingene promoter (Ad-ßA3/A1-cry-HSV1TK), a αB-crystallinpromoter (Ad-αB-cry-HSV1TK). LECs infected by Ad-HSV1TK undergocell death in the presence of the prodrug ganciclovir (GCV).Lens capsules are cultured for 4 weeks and examined every 5days for LECs proliferation state.Results: Sixty pig lens capsuleswere isolated. Twenty were used to assess the conditions oforgano-culture and infections by the recombinant adenoviruses.We only observed GFP expression in LECs infected by adenovirusesexpressing GFP under the control of αB-crystallin, ßA3/A1-crystallinor Major Intrinsic Protein promoter. No PCO of lens capsulecultures by LECs were observed for a viral dose of 7.105 and5.106 pfu Ad-αBcry-HSV1TK in the presence of GCV compared tothe lens capsules controls covered by LECs in 10 days.Conclusion:Although further studies will be necessary, the delivery ofa suicide gene specifically expressed in LECs by recombinantadenovirus may be considered as a preventive measure for PCOwhen used at time of primary cataract surgery.